title: Improved methodology to induce hyperoxaluria without treatment using hydroxyproline.
abstract: The use of hydroxyproline (HP) to generate hyperoxaluria in the rat is a problem because it is impossible to separate the effect of oxalate on renal injury from the effects of HP and the large array of metabolic intermediates formed when HP is converted to oxalate. Previously, the Dahl salt-sensitive (SS) and Brown Norway (BN) rat strains were studied to determine genetic control of resistance or susceptibility to HP-induced renal injury and crystal deposition. To develop a better model to induce hyperoxaluria without causing injury from HP metabolites, animals were fed a diet containing various levels of added oxalate (0, 1, 2, 3, or 5%). After 5 weeks rats were killed and the kidneys were removed for microscopic evaluation of tubule changes and crystal deposition. The 3 and 5% oxalate-fed groups had a substantial increase in urine oxalate, about 50 and 140 μmol/g body weight over controls, respectively. Both the SS and BN 3% oxalate-fed animals showed only slightly elevated tubule area and no crystal deposition. However, BN animals fed 5% oxalate had a dramatic increase in their percent tubule areas compared to control BN rats and treated SS rats. Crystal deposition in the kidneys was only observed in the 5% oxalate-fed groups. The BN kidneys demonstrated a threefold higher crystal deposition compared to oxalate-fed SS rats. We conclude that oxalate-supplemented food is a better method of producing hyperoxaluria in the rat than using HP which may introduce metabolic intermediates injurious to the kidney.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Wiessner
authors.forename: Michael R
authors.initials: MR
authors.lastname: Garrett
authors.forename: Linda Y
authors.initials: LY
authors.lastname: Hung
authors.forename: David F
authors.initials: DF
authors.lastname: Wille
authors.forename: Neil S
authors.initials: NS
authors.lastname: Mandel
mesh_terms: D000818:Animals; D003460:Crystallization; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000008:administration & dosage / Q000633:toxicity; D006959:Hyperoxaluria / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D019815:Oxalic Acid / Q000008:administration & dosage / Q000633:toxicity / Q000652:urine; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl
chemical_list: D019815:Oxalic Acid; D006909:Hydroxyproline